PROJECT SUMMARY: A key component of this P30 application is the ‘Personalized Model System Core’. The models will include the patient-specific cultures derived from intestinal epithelia (enteroids) and the induced pluripotent stem cells (iPSCs) from myofibroblasts. These patient specific cultures will be used to study CFTR function and fluid homeostasis, and the information obtained will be used towards personalized treatment options. The Personalized Model System core will develop and bank these models, develop and validate the assays for CF/CFTR research, and distribute the resources to researchers worldwide. The long-term goal of this core is to use models derived from the patient to facilitate his/her personalized therapy. Specific Aim 1. To provide well- characterized CF patient-specific enteroids (small bowel and colonic) to local, national, and international investigators interested in personalized model systems or CF/CFTR-related research. Specific Aim 2. To provide well-characterized CF patient-specific iPSC-derived tissue from myofibroblasts to local, national, and international investigators interested in personalized model systems. Specific Aim 3. To provide assay services and training to local, national, and international investigators interested in personalized model systems to study the functional involvement of CFTR fluid secretion in intestinal enteroids and spheroids. The Core will create resources and sound services that have important long term clinical implications toward patient-specific therapies for cystic fibrosis. The core will provide training in a variety of state-of-art and innovative techniques including the development of intestinal stem cells cultures, iPSCs technology, high content microscopy, to name a few, to researchers who will be able to use these techniques to study not only CF/CFTR biology but other membrane proteins and their associated diseases.